卵巢高反应对围着床期子宫内膜基因表达谱的影响

目的 研究控制性超排卵过程中卵巢高反应者围着床期子宫内膜基因表达谱的变化。方法 超排卵过程中因出现卵巢高反应而取消胚胎移植的妇女（高反应组，n=4）和有正常生育史的育龄妇女（对照组，n=3），分别于围着床期行子宫内膜组织活检术。HE染色观察子宫内膜组织学改变；基因芯片Affymetrix U133A 2.0筛选差异表达基因，Real-time PCR加以验证；应用生物信息学分析工具PANTHER进行差异表达基因的生物学过程分析。结果 对照组子宫内膜均为分泌中期，高反应组子宫内膜部分腺体发育延迟。筛选出差异表达基因364个，其中上调基因233个，下调基因131个；Real-time PCR验证与子宫内膜功能相关基因OPN、PLA2G2、DPPIV、IGFBP5和 SSAT，每个基因的Real-time PCR结果与芯片检测的信号值呈显著正相关（r=0.44, P<0.01）。PANTHER分析显示，差异表达基因参与细胞因子信号转导和免疫调节等生物学过程。结论 卵巢高反应影响围着床期子宫内膜的基因表达，可能是高甾体激素使子宫内膜接受性降低的机制之一。

Gene expression profiles of peri-implantation endometrium of high responders during controlled ovarian hyperstimulation

Objective To investigate the gene expression profiles of peri-implantation endometrium of high responders during controlled ovarian hyperstimulation. Methods High responders with cancelled embryo-transfer during controlled ovarian hyperstimulation (high responder group, n=4) and healthy fertile volunteers (control group, n=3) were performed endometrial biopsies during peri-implantation. Histologic changes of endometrium were observed by HE staining, genes of differential expression were screened with microarrays Affymetrix U133A 2.0 and identified by Real-time PCR. The biological process analysis was performed by online biological information analysis tool PANTHER. Results The ehdometrium was in mid-secretory phase in control group, while development delay was found in some glandular organs in endometrium of high responder group. Three hundred and sixty-four genes of differential expression were screened, among which 233 were up-regulated genes and 131 were down-regulated genes. OPN, PLA2G2, DPPIV, IGFBP5 and SSAT were identified as endometrial function-related genes, whose Real-time PCR findings were positively correlated to gene signal values detected by microarray(r=0.44, P<0.01). PANTHER analysis indicated that genes of differential expression participated in the biological processes of cytokine signal transduction and immunological regulation. Conclusion Ovarian high response affects the gene expression profiles of peri-implantation endometrium, which may be one of the causes of sub-optimal endometrial receptivity.